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Inception of devices engineered to insert medication into the mucosal lining overcomes limitations of traditional administration methods. Mechanical forces from such microneedle insertions can affect tissue and cellular behavior, particularly mechanotransduction markers. This study investigates the effects of needle insertion in gastric tissue to inform the design of alternative drug delivery devices. Experimental and computational approaches were utilized, using tension and radial compression tests on porcine gastric tissue to inform a finite element analysis (FEA) model. This model was validated with atomic force microscopy (AFM)-based micro-indentation to examine stiffness variations near the insertion site, and yes-associated-protein-1 (YAP-1) expression was analyzed to assess cellular mechanotransduction. AFM results revealed a distance-dependent decrease in tissue stiffness from the insertion site (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), with significant differences in needle geometry (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). The FEA model correlated well with AFM findings, confirming its validity for further cellular simulations. Mechanical stresses from needle insertion were shown to propagate through the tissue, affecting both cytoplasmic and nuclear stress distributions and altering nuclear morphology near the insertion site. The blunt needle produced a higher localized stress field compared to the sharp needle. Additionally, YAP-1 expression was lower in the injected samples than in control samples showing distance-dependent responses observed. This study demonstrates a validated model linking tissue mechanics and cellular responses, highlighting how needle geometry impacts gastric tissue mechanics and mechanotransduction, providing insights essential for designing gastric drug delivery devices.<\/jats:p>","DOI":"10.1007\/s10237-025-01986-z","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T12:33:54Z","timestamp":1755088434000},"page":"1633-1651","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanobiology of gastric needle insertions: a combined experimental and numerical study"],"prefix":"10.1007","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7171-2599","authenticated-orcid":false,"given":"Sif Julie","family":"Friis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torben Str\u00f8m","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette","family":"Poulsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0189-992X","authenticated-orcid":false,"given":"Peter","family":"Helding Kvist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3075-4300","authenticated-orcid":false,"given":"Ansgar","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5792-2845","authenticated-orcid":false,"given":"Hans","family":"Gregersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2442-1443","authenticated-orcid":false,"given":"Jens","family":"Vinge Nygaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"1986_CR1","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1038\/s41591-019-0598-9","volume":"25","author":"A Abramson","year":"2019","unstructured":"Abramson A et al (2019a) A luminal unfolding microneedle injector for oral delivery of macromolecules. 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HG is working as a consultant for Novo Nordisk A\/S and receives remuneration.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The majority of the porcine stomachs in this study were collected at a local abattoir and taken from the carcasses of animals slaughtered for food purposes. A single porcine stomach was collected from the animal facility at Charit\u00e9 (Berlin, Germany) for the current study. This pig was euthanized for another study. Hence, no animals were killed solely for this research. The animal experiments did comply with and were carried out in accordance with ethical guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}